曲格列酮对人网膜前脂肪细胞分化过程中基因表达和脂肪细胞因子分泌的影响

Effect of Troglitazone on Gene Expression and Secretion of Adipocytokines during Human Omental Preadipocytes Differentiation

采用胶原酶消化法分离培养人大网膜前脂肪细胞。曲格列酮干预细胞,油红O染色鉴定分化状态,ELISA测定脂肪细胞因子分泌水平,RT-PCR观察分化转录因子和脂肪细胞因子mRNA表达,以期从内脏脂肪的储脂和内分泌功能角度探讨噻唑烷二酮类药物的作用机制。结果发现,曲格列酮能促进人前脂肪细胞分化,提高脂肪细胞储脂能力;显著增加脂联素分泌;调节瘦素分泌;抑制抵抗素分泌,提示噻唑烷二酮类药物可通过调节脂肪细胞因子谱改善机体胰岛素抵抗和炎症状态。其作用机制可能主要通过促进PPARγ2、C/EBPα和脂蛋白酯酶(Lipoprotein lipase,LPL)等基因的表达。脂肪细胞的增加和瘦素分泌的改变可能部分解释噻唑烷二酮类药物增加体重的负面效应。

Omental preadipocytes were primarily cultured and interfered by collagenase digestion. Troglitazone intervention cells, oil red O staining differentiation, ELISA determination of the level of secretion of adipocytokines, RT-PCR observation for the differentiation transcription factors and fat cell factor mRNA expression, the purpose is to study mechanism of thiazolidinediones from the perspective of the visceral fat storage lipid and endocrine. The results showed that troglitazone increased the human preadipocyte differentiation, improved visceral adipose tissue storage lipid capacity; it can significantly increase adiponectin secretion; regulate leptin secretion; inhibite resisting factor secretion. This suggested that thiazolidinediones improved insulin resistance and inflammation in the body by regulating adipocytokines spectrum. The main mechanism is to promote PPARγ, C/EBPα and lipoprotein lipase （LPL） of mRNA. The increase in fat cells and changes in leptin secretion may partly explain the negative effects of thiazolidinediones in increasing body weight.